In vivo tests: Prick test, scratch test, intradermal test vivo test.pdf · In vivo test methods...
Transcript of In vivo tests: Prick test, scratch test, intradermal test vivo test.pdf · In vivo test methods...
15.08.2013
In vivo tests: Prick test, scratch test, intradermal test
Erlangen, 26.7.2013
Diagnostic algorithm
1.) hx taking
2.) diagnostic measures
skin testing
laboratory tests
provocation tests
3.) result assessment (relevance ?)
Bousquet J et al. Practical guide to SPTs in allergy to aeroallergens. Position paper. Allergy 2012; 67: 18-24.
concordant, if allergen source is
In vivo test methods
skin prick test (commercial test solutions, fresh material)
scratch test
intradermal (=intracutaneous) test
open patch test/rub test
provocation tests
negative (0.9% sodium chloride) control
positive control (1.0% or 0.1% histamine hydrochloride for SPT and 0.01% for the intracutaneous test)
emergency plan (rescue medication at hand)
Skin prick test (SPT)
Peyps J. Br. J Hosp Med. 1975; 14: 412-417.Dreborg S. Allergy 1989; 44 (Suppl. 10): 31-7.Masse MS et al.. Allergy 2011; 66: 1415-19.
technique: disposable single-use metal needle or lancet crossing the drop, bevel up, before making a
slight infringement of the skin without causingbleeding
constant technique (pressure and time of applied pressure)
10fold increase of allergen concentration: 2-2.5 fold increase of wheal area
duplicate SPT for routine, quadruplicate forscientific purposes (variation of MWD < 20%)
SPT is recommended as the best skin test (safety, technical performance, reproducibility)
Skin scratch test and scratch chamber testtechnique:
1 mm lancet
5 mm skin scratch-without bleeding
Niinimäki A. Contact dermatitis 1987; 16:11-20.Dreborg S, Frew A & EAACI Subcommittee on skin tests. Allergy 1993 (suppl) 48-82.
Osterballe M et al. Allergy 2003: 58: 950-953.Suzuki Y et al. Arerugi 2009; 58:1619-28.
with or without 12 mm Finn chamber
scratch test: low specificity
scratch chamber: low sensitivity forfresh apple (30%) and birch (60%) versus SPT (80%/100%)
not recommended
Skin scratch test
technique: 1 mm lancet 5 mm skin scratch-without
bleeding with or without 12 mm Finn
chamber
Scratch chamber: lowsensitivity for fresh apple(30%) and birch (60%) versusSPT (80%/100%)
not recommended
scratch test skin prick test
0.1% histamine
0.9 % sodium chloride
birch
carrot
cat
7
Intradermal test(higher sensitivity than SPT)
technique: 26 gauge needle 1ml syringe 0.02-0.05 ml test solution test solutions: preferentially stabilized by addition of 0.03% human serum
albumin; glycerol concentration ≤ 2%; 0.1-1% of the SPT-solution
more reproducible and higher sensitivity than SPT for testing with low potency extracts when SPT was negative (despite indicative hx) for aeroallergen extracts: no advantage over SPT.
Dreborg S, Frew A & EAACI Subcommittee on skin tests. Allergy 1993 (suppl) 48-82.
8
6. 1.06. 1.0
5. 0.15. 0.1
4. 0.014. 0.01
3. 0.001 3. 0.001
2. 0.00012. 0.0001
1. 0.000011. 0.00001
reactivityYellowjacketvenom[μg/ml]
reactivityHoney beevenomconcentration[μg/ml]
Intradermal test(higher sensitivity than SPT)
Reading (semiquantitative)
>40>15>20>6pseudopods
++++
21-4011-1511-204-6+++
11-206-106-103++
5-103-53-52-3+
<5<3<3<2
intradermalerythema(mm )
intradermalwheal(mm )
SPTerythema(mm )
SPTwheal(mm )
Ring J. Angewandte Allergologie. 1988
Reading (semiquantitative)
≥ 15≥ 6pseudopods
++++
+++
≥ 4 - < 5++
≥ 3 - < 4+
< 5< 3(+)
intradermalwheal(mm )
SPTwheal(mm )
AWMF-Guideline No. 061/026; 2009
0 0
≥ 5 - < 6
≥ 5 - < 8
≥ 8 - < 11
≥ 11 - < 15
Reading (quantitative)
Mean wheal diameter (MWD): (D + d)/2,D = the longest diameter of the wheal,d = the longest diameter orthogonal to D
Longest wheal diameter (LWD): D
→ „The longest wheal diameter alone is a better surrogate markerof the wheal surface, in comparison with the mean diameter, but also easierand faster to measure. Therefore, it seems to be preferable for SPT evaluation.“
D
d
Positive: ≥ 3 mm MWD (SPT), ≥ 5 mm MWD (intradermal test),
Dreborg S, Frew A & EAACI Subcommittee on skin tests. Allergy 1993 (suppl) 48-82.Konstantinou GN et al. Int Arch Allergy Immunol 2010; 151:343–345.van Kampen V et al.. EAACI position paper: SPT in the diagnosis of occupational type I allergies. Allergy 2013; 68: 560-584.
for occupational allergens:≥ 1.5 mm MWD (SPT)
Longest wheal diameter
Bousquet J et al. Practical guide to SPTs in allergy to aeroallergens. Position paper. Allergy 2012; 67: 18-24.
In vivo testing with non-standardized agents
sterile, non-infectious material
no intradermal tests with colored agent(iatrogenic tattoo)
dilution series
controls (allergic reaction, if ≤ 2/10 individuals show positive reaction)
be aware of national legal requirements(e.g, Germany: § 67: duty of disclosureto the inspecting authority)
medical history
concordance?
test results
Assessment
Dreborg S. Allergy 1989; 44 (Suppl. 10): 31-7.
not all individuals with detectable allergen-specific IgE show clinical allergy at contact
some develop clinical allergy later and in some the test may remain positive after clinical symptoms have disappeared.
sensitization ╪ clinical allergy
Assessment
(positive test) (clinical symptoms)
treatment
Kuehn HS et Gilfillan AM. Immunol Lett 2007; 113: 59-69
medical history positive
?
test results negative
What if…..
Causes for false-negative test results
Mahler V. Prick and Intracutaneous Testing and IgE Testing In: Kanerva's Occupational Dermatology. Springer, 2nd edition 2012; pp 943-960.
(False-)negative test result due to in vivo
incomplete test material (missing components) +
incorrect technique +
cut-off set to high -
allergen-specific blocking IgG-antibodies -
refractory phase (following antibody depletion in severeanaphylactic reactions)
+
local IgE-production +
different immunological mechanism (e.g. late-phasereaction) or non-immunological mechanism inducessymptoms
+
concomitant medication (systemic H1-blocker, certainH2-blockers (ranitidine), ketotifen, phenothiazine-derivatives, tricyclic antidepressants, ß-adrenergicagonists, high dose corticosteroids, topical steroids in test site)
+
skin alterations due to underlying disease (diabeticneuropathy, chronic hemodialysis)
+
incomplete history concerning the culprit allergenexposure
+
Incomplete SPT material (missing components):occupational allergen sources
n=115 individuals with baker´s asthma 4 commercial SPT-solutions (wheat/rye flour) specificity: 86-100% sensitivity (SPT compared to allergen-specific bronchial
provocation): rye flour (SPT-solution): 40-50%.wheat flour (SPT-solution): 45-67%
30-60% false-negative
→„Improvement and standardization of SPT extracts for wheat and rye flour is highly recommended.“
van Kampen V et al.. Allergy 2013; 68: 560-584.van Kampen V et al.. Allergy 2013; 68: 651-658.Sander I et al.. Allergy 2004; 59: 95-98. Focke M et al. Eur J Clin Invest 2009; 39: 429–436
immunological mechanisms: type I-type IV (Coombs& Gell)
in vivo and in vitro tests: frequently false-negative(despite existing allergy)
missing components (metabolites)/inadequate allergen presentation
Incomplete test material (missing components):drug allergies
urticarial macular/papular erythemamultiforme-like
Fixed-drug eruption
type I type IV type III/IV type IV
for antibiotics
for perioperative drugs
for selected drugs
Nonirritating test concentrations for SPT an IDT
Brockow et al.. Skin test concentrations for systemically administered drugs- an ENDA/EAACI Drug Allergy Interest Group position paper. Allergy 2013; 68:702-12.
Non-immunological mechanism:
NSAIDS
local anaesthetics
food additives
SPT and intradermal test negative
dose-dependant
provocation tests (route similar to regular application)
objective: find tolerated agent (therapeutic dose)
medical history negative
?
test results positive
What if…..
Causes for false-positive test results
Mahler V. Prick and Intracutaneous Testing and IgE Testing In: Kanerva's Occupational Dermatology. Springer, 2nd edition 2012; pp 943-960.
+clinically silent cross-reactivity to homologous allergens (different primary sensitizing allergen source)
-carbohydrate specific IgE-binding
-non-specific IgE-binding in individuals with total IgE > 1000 IU/ml
+skin condition of individual is unfit for testing (eczematous skin, urticaria factitia)
+incorrect technique (distance of test sites is to low; reuse of test lancet)
+test substance is a non-specific mast cell secretagogue
+test substance naturally contains histamine
+contaminated test material
in vivo(False-)positive test result due to
Allergic to sodium chloride ?
62yo cleaning woman previous SPT positive presentation for medical report on„allergy against sodium chloride“ objective: early retirement
no relevance(false-positive in vivo test)
Summary
skin prick test is the test of choice
scratch test is obsolet
intradermal test for low potency allergens
use disposable metal test device (needle, lancet)
the longest wheal diameter is feasible for recording of test reactions
standardized extracts are available for most aeroallergens
in vivo testing of occupational allergens and drugs follows itsown rules
false-positive and false-negative test results may occur